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Genetic counseling: Familial Adenomatous Polyposis
Familial Adenomatous Polyposis Contracting *Introductions *Assess main concerns of patient **How did the referral to the Hereditary Cancer Program come about? **What do they hope to gain from the session? *Assess knowledge of diagnosis **What do they already know about FAP? **What do they already know about hereditary cancer? *Overview of today's agenda **Restate patient's concerns **Medical history, family history, genetics of hereditary cancer, inheritance pattern and recurrence risks, testing options and limitations Review Medical and Family History *Medical History **Any major health concerns? **Surgeries or hospitalizations? **Colon cancer screening? *Family History **Other individuals with any type of cancer? **Focus on colorectal cancers, pancreatic cancer, thyroid cancer, brain cancer, as well as desmoid tumor cysts in the mandible **Screening practices of other family members? **Family thoughts about the cause of cancer? **Family experiences with cancer? General Cancer Information *All cancer is caused by a mixture of genes and environment **All cancer is genetic, but not all cancer is hereditary **Most cancers (90-95%) are sporadic *Cancer Genetics **cells in our bodies are constantly growing and dividing **certain genes control/regulate cell growth **a change in these genes will result in a cell that grows out of control = cancer ***the changes occur due to damage to the genetic material ***DNA, genes, chromosomes ***DNA contains the instructions for making proteins, which determine what cells do and regulate how we develop ***the DNA must be copied each time a cell divides ***sometimes a copying mistake, a typo, can occur **Hereditary forms of cancer involve a person inheriting one non-working copy of a gene ***one step closer to developing cancer than a person with two working copies (therefore it is called an inherited predisposition) ***features of hereditary cancer include: ****earlier than expected age of onset ****multiple generations affected ****bilateral or multiple primary cancers ****siblings affected General Colorectal Cancer Information *Statistics **third most common form of cancer **most colorectal cancers are sporadic **6% (1/16) lifetime risk for colon cancer in the general population **most individuals diagnosed over the age of 50 ***average age of diagnosis is 67 **risk factors include aging, diet, previous history of adenoma, colorectal cancer, or inflammatory bowel disease **about 5% of colon cancer is due to a hereditary predisposition ***HNPCC (4%) and FAP (1%) are the two known forms ***more likely to occur before the age of 50 FAP-specific information *Clinical Characteristics **hundreds to thousands of adenomatous polyps in the colon and rectum at an early age ***90% of carriers will have polyps by the age of 20 ***virtually all carriers will have polyposis by the age of 35 ***malignancy will occur in virtually 100% of carriers by the age of 40-50 **Classic FAP diagnosis requires a minimum of 100 polyps **Attenuated FAP generally has polyps developing at a later age and occurring proximally (though they may be found throughout the colon and rectum) **Gardner Syndrome (a phenotypic variant of FAP) is characterized by polyposis plus soft tissue tumors of the skin (epidermal cysts), osteomas, desmoid tumors, and supernumerary teeth **Colon cancer (average age of onset = 39 in FAP patients) is virtually inevitable if the colon is not removed prophylactically *Genetics **due to mutations in the adenomatous polyposis coli (APC) gene ***on chromosome 5q ***autosomal dominant inheritance ***a tumor suppressor gene ***both alleles must be mutated for function to be lost ***more than 700 mutations have been reported ***most lead to truncation of the APC gene ***most families have separate and distinct mutations ***de novo mutations account for about 30% of FAP cases ***mutations in the germ cell of a parent *Screening and Management **annual flexible sigmoidoscopy or colonoscopy beginning at age 10-12 ***if polyps are found, they should be removed and a colectomy considered **routine upper GI endoscopy **if no polyps found by the age of 25, reduce screening frequency to once every two years until age 35, then every three years until age 50, then every 3-5 years after age 50 **even if a colectomy is performed, life-long surveillance is required due to the association with extracolonic primary malignancies **the effectiveness of chemoprevention is not well established ***the possibility of NSAID's are currently being evaluated in trials *Associated Risks **primary adenomas and carcinomas of the duodenum **desmoid tumors (in 10% of FAP patients) **osteomas **thyroid carcinoma **brain tumors **hepatoblastoma **hepatopancreatic tumors **gastric fundic gland polyps **CHRPE (congenital hypertrophy of the retinal pigment epithelium) *Risk Assessment **autosomal dominant inheritance (50% chance of inheriting it from an affected parent) **30% are de novo mutations **penetrance is virtually 100% by the age of 40 Genetic Testing for FAP *Two indications: **testing an individual who has a clinical diagnosis of FAP **testing an individual who is a relative of an established mutation carrier ***testing an unaffected family member in the absence of an established mutation has a significant risk of a false negative result ***since each family tends to have a unique mutation *Protein Truncation Assay **the most common commercial test **able to identify most classical FAP mutations **once a mutation is identified, PTA is virtually 100% accurate in classifying carriers *Denaturing Gradient Gel Electrophoresis (DGGE) **an alternative method that may be informative when PTA is not **involves direct sequencing of a region in which truncation is identified in an affected family member *Gene Sequencing **maybe used when no other tests are informative **uses linkage analysis or flanking polymorphic genetic markers **requires multiple requires a firm diagnosis of FAP in multiple family members ***is therefore useless in the 30% of cases which are de novo Resources *American Cancer Society :800-227-2345 :www.cancer.org *CancerCare :800-813-4673 :www.cancercare.org References *www.geneclinics.org *www.cancer.org *FAP background and screening macros (B.C. Hereditary Cancer Program) *Module 6: "Hereditary Colorectal Cancer Syndromes" p 43-55 *"Hereditary Colorectal Cancer: A Guide for Patients and Their Families" by The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry (Mount Sinai Hospital, Toronto, Canada) FAP resources *Colon Cancer Alliance :175 Ninth Avenue :New York, NY 10011 :Phone: 212-627-7451; toll-free helpline 1-877-422-2030 :Fax: 425-940-6147 :Email: kelly@ccalliance.org :www.ccalliance.org *Colorectal Cancer Network :PO Box 182 :Kensington, MD 20895-0182 :Phone: 301-879-1500 :Fax: 301-942-7145 :Email: semicolonclub@yahoo.com :www.colorectal-cancer.net *Genetics of Colorectal Cancer (PDQ) :A service of the National Cancer Institute :www.cancer.gov/cancer_information *Hereditary Colon Cancer Association (HCCA) :3601 N 4th Ave, Suite 201 :Sioux Falls, SD 57104 :Phone: 800-264-6783; 605-373-2067 :Fax: 605-336-6699 :Email: hcca@dtnet.com :www.hereditarycc.org *IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer) :PO Box 11 :Conyngham, PA 18219 :Email: impacc@epix.net *American Cancer Society :1599 Clifton Rd NE :Atlanta, GA 30329 :Phone: 800-227-2345 :www.cancer.org/index.html *Collaborative Group of the Americas for Inherited Colorectal Cancer :www.fascrs.org/ascrs-cancer-reg.html Notes The information in this outline was last updated in 2002. This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.